Small Cell Lung Cancer Treatment Protocols 

Updated: Mar 21, 2019
Author: Marvaretta M Stevenson, MD; Chief Editor: Nagla Abdel Karim, MD, PhD 

Treatment Protocols

Treatment protocols for small cell lung cancer (SCLC) are provided below, including first-line therapy, therapy for limited-stage disease, and therapy for extensive-stage disease.

Treatment recommendations for limited-stage SCLC

Stages I-III disease:

  • Limited-stage disease is typically treated with systemic therapy, with or without radiation therapy[1]

  • Chemotherapy and radiation therapy are typically given concurrently, but can also be given sequentially for limited-stage disease in patients unable to tolerate concurrent chemoradiation; chemotherapy is given first, followed by radiation therapy because of the high rate of responsiveness to chemotherapy for SCLC[2, 1]

  • A select group of patients may be eligible for surgical resection.  Clinical stage I - IIA (T1 - 2, N0, M0) patients who are surgical candidates should undergo pathological mediastinal staging to determine if there is medastinal lymph node involvement. 

    • Patients with pathologically negative medastinal lymph nodes should go on to lobectomy with mediastinal lymph node dissection or sampling.

    • Patients found to have pN0 disease at the time of surgical resection should receive adjuvant systemic therapy (see options below)

    • Patients found to have pN1 or pN2 disease should receive systeic therapy +/- mediastinal radiation therapy

Concurrent chemotherapy recommendationswith radiation for limited-stage disease include:

  • Cisplatin 60 mg/m2 IV on day 1 plusetoposide 120 mg/m2 IV on days 1-3 every 21 - 28d[3, 1]

  • Cisplatin 75 - 80 mg/m2 IV on day 1 plus etoposide 100 mg/m2 IV on days 1-3 every 21 - 28d[4, 1]

  • Cisplatin 25 mg/m2 IV on days 1 - 3 plus etoposide 100 mg/m2 IV on days 1-3 every 21 - 28d [1]

  • Carboplatin AUC 5-6 IV day 1 plus etoposide 100 mg/m2 IV days 1-3 every 21 - 28d[5, 1]

  • Chemotherapy should be given up to 4 - 6 cycles

  • Radiotherapy for limited-stage disease should start with cycle 1 or 2 of chemotherapy

Chemotherapy recommendations for patients not able to tolerate concurrent chemotherapy and radiation:

  • Patients with limited-stage (stages I–III) disease who are not able to tolerate chemotherapy and radiation concurrently should be treated with chemotherapy as first-line therapy

  • Cisplatin 60-80 mg/m2 IV on day 1 plus etoposide 80-120 mg/m2 IV on days 1-3 every 21-28d[3, 4] or

  • Carboplatin AUC 5-6 IV on day 1 plus etoposide 80-100 mg/m2 IV on days 1-3 every 28d[6] (see also the Carboplatin AUC Dose Calculation [Calvert formula] calculator)

First-line chemotherapy for extensive-stage disease

Stage IV disease

The following treatment recommendations should be given for a maximum of 4-6 cycles:

  • Atezolizumab 1200 mg IV on day 1 plus carboplatin AUC 5 on Day 1 plus etoposide 100 mg/m2 IV on days 1-3 every 21d x 4 cycles; follow with maintenance atezolizumab every 21d[7]

  • Cisplatin 60-80 mg/m2 IV on day 1 plus etoposide 80-120 mg/m2 IV on days 1-3 every 21-28d[8, 9, 10, 11, 12, 13, 14, 15]

  • Carboplatin AUC 5-6 IV on day 1 plus etoposide 80-100 mg/m2 IV on days 1-3 every 28d[15, 16, 17, 18]

  • Cisplatin 60 mg/m2 IV on day 1 plusirinotecan 60 mg/m2 IV on days 1, 8, and 15 every 28d[10, 13, 14]

  • Cisplatin 30 mg/m2 IV on days 1 and 8 or 80 mg/m2 IV on day 1 plus irinotecan 65 mg/m2 IV on days 1 and 8 every 21d[9, 11]

  • Carboplatin AUC 5 IV on day 1 plus irinotecan 50 mg/m2 IV on days 1, 8, and 15 every 28d[16, 18]

  • Carboplatin AUC 4-5 IV on day 1 plus irinotecan 150-200 mg/m2 IV on day 1 every 21d[19, 20, 21]

  • Cisplatin 25 mg/m2 IV on days 1 - 3 plus etoposide 100 mg/m2 IV on days 1-3 every 21 - 28d [1]

  • Cyclophosphamide 800-1000 mg/m2 IV on day 1 plusdoxorubicin 40-50 mg/m2 IV on day 1 plusvincristine 1-1.4 mg/m2 IV on day 1 every 21-28d[22, 23, 24]

Second-line chemotherapy for relapsed or refractory disease

Stage IV disease[9] :

  • Second-line chemotherapy is given for at least 4-6 cycles but can be given until disease progression as tolerated in some cases

  • Patients who have relapsed disease more than 6mo after completing first-line chemotherapy can be treated with that original first-line regimen (typically a platinum-based doublet) again, with an expected response rate of 62-100%[2, 1]

Systemic therapy recommendationsfor relapsed or refractory SCLC include:

  • Etoposide 50 mg/m2 PO daily for 3wk every 4wk[25]

  • Topotecan 2.3 mg/m2 PO on days 1-5 every 21d[26, 27, 28]

  • Topotecan 1.5 mg/m2 IV on days 1-5 every 21d[26, 27, 29]

  • Carboplatin AUC 5 IV on day 1 plus irinotecan 50 mg/m2 IV on days 1, 8, and 15 every 28d[16, 18]

  • Carboplatin AUC 4 - 5 IV on day 1 plus irinotecan 150-200 mg/m2 IV on day 1 every 21d[19, 20, 21]

  • Cisplatin 30 mg/m2 IV on days 1, 8, and 15 plus irinotecan 60 mg/m2 IV on days 1, 8, and 15 every 28d[30]

  • Cisplatin 60 mg/m2 IV on day 1 plus irinotecan 60 mg/m2 IV on days 1, 8, and 15 every 28d[10, 14]

  • Cisplatin 30 mg/m2 IV on days 1 and 8 or 80 mg/m2 IV on day 1 plus irinotecan 65 mg/m2 IV on days 1 and 8 every 21d[9, 11]

  • Paclitaxel 80 mg/m2 IV weekly for 6wk every 8wk[31]

  • Paclitaxel 175 mg/m2 IV on day 1 every 3wk[32]

  • Cyclophosphamide 800-1000 mg/m2 IV on day 1 plusdoxorubicin 40-50 mg/m2 IV on day 1 plusvincristine 1-1.4 mg/m2 IV on day 1 every 21-28d[1]

  • Pembrolizumab 200 mg IV every 3 weeks until disease progression[33]

  • Nivolumab 240 mg IV every 2wk or nivolumab 480 mg IV every 4 wk until disease progression[34, 1, 35]

  • Nivolumab 1 mg/kg IV plus ipilimumab 3 mg/kg IV every 21 days for 4 cycles followed by nivolumab maintenance (240 mg IV every 2wk or nivolumab 480 mg IV every 4 wk)[1, 34, 35]

  • Institution Review Board (IRB)–approved clinical trial

Special considerations

See the list below:

  • Patients with mixed SCLC/non-SCLC histology should be given the same treatment as patients with SCLC[1, 2]

  • Prophylactic cranial irradiation is recommended for SCLC patients with a complete or partial remission (total of 25 Gy in 10 fractions or 30 Gy in 10-15 fractions)[1, 2]

  • Thoracic radiation therapy should be considered for patients with extensive stage disease after they complete systemic therapy[1]

  • Dose-dense or dose-escalation chemotherapy regimens are not recommended outside of a randomized clinical trial[1, 2]

  • Patients with brain metastases can receive chemotherapy prior to brain radiation due to high response rates with chemotherapy[1, 2]

  • A study evaluating treatment of patients with stereotactic body radiation therapy concluded that it is a promising alternative to surgery for patients with stage I non-SCLC[36]